Our studies are directed towards an understanding of the metabolic pathogenesis of cystic fibrosis and by such studies we hope to come to an understanding of the disease which will allow us to diagnose the heterozygote and to suggest regimens for control of the symptoms in the homozygote. During the coming year we plan to isolate and purify factor(s) from the saliva of selected patients with cystic fibrosis whose secretions do exhibit an inhibition of respiration in the brine shrimp assay. Hopefully through the investigation of single patients we may be able to determine why the saliva of other patients does not reflect an inhibition on this system. We also plan to continue our studies of the metabolism of fibroblasts from cystic fibrosis patients using two-dimensional acrylamide gel electrophoresis of plasma membranes and soluble proteins in order to determine both qualitative and quantitative differences in the synthesis and turnover of proteins resolved by this more sensitive system. We will extend our investigations of the polyamines to a study of their metabolism by fibroblasts from normals and patients with cystic fibrosis. BIBLIOGRAPHIC REFERENCE: Changus, J.E., Quisell, D.O., Sukup, M.R. and Pitot, H.C. Studies on the synthesis of plasma membrane proteins of fibroblasts from patients with cystic fibrosis. Am. J. Path. 80: 317-328, 1975.